Granulocyte colony-stimulating factor induces hFc gamma RI (CD64 antigen)-positive neutrophils via an effect on myeloid precursor cells

Abstract

In this study we have examined hFc gamma RI expression during myelopoiesis. Normal bone marrow (BM) cells were found to express hFc gamma RI up to the metamyelocyte stage. A different Fc gamma RI expression pattern was observed in an in vitro model of myelopoiesis. Purified CD34-positive BM cells, cultured for 12 to 14 days with granulocyte colony-stimulating factor (G-CSF), differentiate into a population of mature granulocytic cells. In these cultures, in which hFc gamma RI was virtually absent on the initial CD34-positive BM cells, hFc gamma RI was strongly induced by G-CSF after only 5 days. During final maturation the cells remained hFc gamma RI positive. This expression was confirmed functionally by antibody-sensitized erythrocytes (EA)-rosette assays. Moreover, the mature myeloid cells were found to express mRNA encoding for hFc gamma RI, whereas reverse- transcriptase polymerase chain reaction analysis showed that both hFc gamma RIA and hFc gamma RIB genes were expressed. In contrast, on peripheral blood (PB) polymorphonuclear neutrophil leukocytes (PMN) the in vitro effect of G-CSF as to hFc gamma RI induction was limited. Therefore, we conclude that, with respect to hFc gamma RI expression on PMN, G-CSF acts on myeloid precursor cells rather than on mature cells. This conclusion could be strengthened by in vivo administration of a single dose of G-CSF to a healthy volunteer. After a 12-hour lag time, hFc gamma RI expressing PMNs were detected in the peripheral blood. This study shows that hFc gamma RI is an early myeloid differentiation marker that is lost during normal final maturation. However, committed myeloid progenitor cells can be strongly induced by G-CSF to express hFc gamma RI, ultimately resulting in mature granulocytic cells expressing the high-affinity receptor for IgG. This expression may have important consequences for the functional capacity of these cells.

Ex vivo neutrophil function in response to three different doses of glycosylated rHuG‐CSF (Lenograstim)

“…Our data shows that FcRIII expression was reduced with all doses of rHuG-CSF by 96 h, for both FMLP and Staphylococcus epidermidis stimulated and unstimulated PMN, although these decreases were not statistically significant. This down-regulation of FcRIII expression in response to rHuG-CSF appeared to correlate with an increase in FcRI levels, which agrees with the observations of previous G-CSF studies with human PMN (Kerst et al, 1993b;Spiekermann et al, 1994). The exact mechanism and biological significance of this reduced surface expression of FcRIII is still unclear, although several theories exist.…”

“…The decrease in FcRIII expression seen in this study could have been due to rHuG-CSF induced proteolytic cleavage. Previous studies have, however, disputed this theory of shedding, the suggestion being that the reduction in FcRIII expression may be due to an increase in circulating immature PMN released from the bone marrow (Kerst et al, 1993b).…”

“…PMN have been shown to strongly express the highaffinity Fc receptor, FcRI (CD64 antigen) following in vivo treatment with G-CSF (Repp et al, 1991;Kerst et al, 1993a, b;Spiekermann et al, 1994) but show unchanged (Repp et al, 1991) or decreased expression of the phosphatidyl inositol (PI) linked Fc RIII (CD16 antigen) receptor (Kerst et al, 1993b;Spiekermann et al, 1994). Bacterial phagocytosis and bactericidal activity against Staphylococcus aureus have been found to be significantly enhanced after preincubation of normal PMN with G-CSF (Roilides et al, 1991).…”

Altered surface expression of effector cell molecules on neutrophils in myelodysplastic syndromes

“…FcRI/CD64 is a specific marker for granulo-monocytic progenitor cells (Olweus et al, 1995). Normal bone marrow cells express CD64 antigen up to the metamyelocyte stage of differentiation (Kerst et al, 1993). In the present study we found that the percentage of FcRI-positive neutrophils was increased in the H-MDS patients.…”

Differential expression of Fc receptors for IgG by monocytes and granulocytes from neonates and adults

“…However, it is unlikely that this cytokine is responsible, since it also enhances FcRI expression by monocytes, which was not observed in these studies. Granulocytes from patients with myeloid leukaemia given granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation showed increased expression of FcRI, which the authors interpreted as due to immature granulocytes which were expressing the higher levels of FcRI [18]. Higher levels of G-CSF have been found in cord compared with adult serum [19].…”